Continuing vs Intermittent Trabectedin-regimen in Patients With Advanced Soft Tissue Sarcoma Experiencing Response or Stable Disease After the 6th Cycle - Full Text View

Purpose

This randomization discontinuation trial will allow for concomitant evaluation of the following:

Side effects and benefits of immediate continuation of Trabectedin after the sixth cycle
Side effects and benefits of a drug holiday

Condition	Intervention	Phase
Soft Tissue Sarcoma Uterine Sarcoma	Drug: Trabectedin Other: Drug: holiday	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Randomized Trial to Evaluate Two Strategies: Continuing Versus Intermittent (Drug-holiday) Trabectedin-regimen in Patients With Advanced Soft Tissue Sarcoma Experiencing Response or Stable Disease After the Sixth Cycle

Resource links provided by NLM:

MedlinePlus related topics: Soft Tissue Sarcoma

U.S. FDA Resources

Further study details as provided by Centre Oscar Lambret:

Primary Outcome Measures:

PFS rate 24 weeks after randomization [ Time Frame: 24 weeks after randomization ] [ Designated as safety issue: No ]
In each arms among non progressive patients after the 6 first cycles of Trabectedin : occurrence of progression or death 24 weeks after the date of randomization. Intention to treat analysis. Centralised radiological review.

Secondary Outcome Measures:

Response rate [ Time Frame: 6, 12 and 18 weeks after randomization ] [ Designated as safety issue: No ]
stabilisation, complete and partial responses according to RECIST 1.1
Progression free survival rates [ Time Frame: 12 and 54 weeks after randomization ] [ Designated as safety issue: No ]
According to RECIST 1.1
Survival rates [ Time Frame: 12 and 24 months after randomization ] [ Designated as safety issue: No ]
Median progression-free and median overall survivals [ Time Frame: Up to 5 years after randomization ] [ Designated as safety issue: No ]
Tolerability [ Time Frame: Up to 30 days after the last study drg administration ] [ Designated as safety issue: Yes ]
According to NCI-CTC V4.0 scale
Clinical and biological predictive factors for non progression at the 6th cycle [ Time Frame: At baseline ] [ Designated as safety issue: No ]
Collected data at baseline : age, gender, comorbidity, disease history, previous treatment, tumor description, biological parameters
Post-randomization cost of care [ Time Frame: For one year after randomization ] [ Designated as safety issue: No ]
Cost of care will be evaluated by macro-costing approach
Self estimation of general health status [ Time Frame: For 1 year after randomization ] [ Designated as safety issue: No ]
Evaluation every 6 weeks by 100-mm-long horizontal visual analog scale (VAS) that ranged from worst imaginable health (as bad as death, 0) to perfect health

Estimated Enrollment:	50
Study Start Date:	February 2011
Estimated Study Completion Date:	February 2017
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Continuation of Trabectedin	Drug: Trabectedin Trabectedin will be administered without drug holiday in Arm A until unacceptable toxicity, progressive disease or patient decision. The treatment beyond disease progression and in case of intolerance will be decided according to investigator discretion. In case of progression after drug discontinuation by patient decision, a re-challenge of Trabectedin is possible.
"Intermittent/holiday" therapy	Other: Drug: holiday A drug-holiday will start after the 6th cycle until disease progression, and then Trabectedin will be re-challenged. Trabectedin will be administered until unacceptable toxicity, second evidence of progressive disease or patient decision.

Detailed Description:

Selection part (220 patients):

Trabectedin (depending on dose reductions : between 1.5 and 1 mg/m²/3 weeks; over 24 hour administration) until progression, intolerance or 6 cycles (according to the SPC of Trabectedin)

Randomized part (50 patients):

After the 6 first cycles, if there is not progression or unacceptable toxicity, the patients will be randomly assigned to continuous or "intermittent/holiday" therapy with CT-scan evaluation every 6 weeks in both arms

Arm A Continuation of Trabectedin (between 1.5 and 1 mg/m²/3 weeks; over 24 hour administration) until progression or intolerance
Arm B "Intermittent/holiday" therapy. Rechallenge of Trabectedin will be implemented in the event of progression; in this case administration of Trabectedin will occur until the second progression or intolerance

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria (for the selection part):

Inoperable or metastatic soft tissue sarcoma and/or uterine sarcoma
Measurable lesions (RECIST 1.1)
Performance status ≤ 2
Age ≥ 18
Normal hematological parameters (polynuclear neutrophils ≥ 1500, hemoglobin level ≥ 9 g/dl, platelets counts ≥ 100,000)
Adequate biological parameters :
Adequate hepatic function (bilirubin ≤ ULN , SGPT/ALT and SGOT/AST ≤ 2.5 x ULN)
Alkaline phosphatases ≤ 2.5 x ULN, If Alkaline phosphatases ≥ 2.5 ULN, hepatic isoenzymes 5-nucleotidases or GGT tests must be performed; hepatic isoenzymes 5- nucleotidases and/or GGT must be within the normal range
Albumin ≥ 25 g/L
Adequate renal function : Serum creatinine ≤ 1.5 x ULN
Creatine phosphokinase ≤ 2.5 x ULN
Adequate central venous access
Pregnant or lactating women or men of reproductive potential must use effective contraceptive methods
Patient covered by government health insurance
Information sheet given to the patient (Patient information sheet 1)

Exclusion Criteria (for the selection part):

Patients that have received more than one regimen of chemotherapy for metastatic or inoperable soft tissue or uterine sarcoma, after the failure/intolerance of doxorubicin and ifosfamide. Maintenance treatment does not count as treatment line
The following histological subtypes : GIST, rhabdomyosarcoma, aggressive fibromatosis, desmoïd tumour, PNET, carcinosarcoma, and all bone sarcomas
Single tumour in an irradiated region
Other malignant tumour over the past five years (except basal cell carcinoma or cervical carcinoma in situ adequately treated)
Currently active bacterial or fungus infection (> grade 2 CTC [CTCAE] Version 4.02). Known HIV1, HIV2, hepatitis B or hepatitis C infections
Presence of known leptomeningeal or brain metastasis
Patients unable to receive corticotherapy
Any circumstance that could jeopardise compliance or proper follow-up during the trial
Pregnant or nursing women

Inclusion Criteria (for the randomized part):

Patient registered in the selection part
Stable tumour or objective response (CR + PR) after 6 Trabectedin (Yondelis®) cycles, according to local assessment
Available copies of thoraco-abdominal and pelvic scan performed prior to the first cycle and after the sixth cycle
Performance status ≤ 2
Patients receiving at least 1 mg/m²/3 weeks of Trabectedin at the time of the sixth cycle
Normal hematological parameters (polynuclear neutrophils ≥ 1500, hemoglobin level ≥ 9 g/dl, platelets counts ≥ 100,000)
Adequate biological parameters :
Adequate hepatic function (bilirubin ≤ ULN , SGPT/ALT and SGOT/AST ≤ 2.5 x ULN)
Alkaline phosphatases ≤ 2.5 x ULN, If Alkaline phosphatases ≥ 2.5 ULN, hepatic isoenzymes 5-nucleotidases or GGT tests must be performed; hepatic isoenzymes 5- nucleotidases and/or GGT must be within the normal range
Albumin ≥ 25 g/L
Adequate renal function : Serum creatinine ≤ 1.5 x ULN
Creatine phosphokinase (CPK) ≤ 2.5 x ULN
Adequate central venous access
Pregnant or lactating women or men of reproductive potential must use effective contraceptive methods
Informed consent form signed by the patient or the patient's legal representative (patient information sheet 2 and informed consent)

Exclusion Criteria (for the randomized part):

Tumour progression (according to RECIST 1.1) during the first six Yondelis cycles
Non-availability of baseline scans prior to the first cycle and following the sixth cycle
Currently active bacterial or fungus infection (> grade 2 CTC [CTCAE] Version 4.02). Known HIV1, HIV2, hepatitis B or hepatitis C infections
Presence of known leptomeningeal or brain metastasis
Creatinine clearance less than 30 ml/min
Patients unable to receive corticotherapy
Any circumstance that could jeopardise compliance or proper follow-up during the trial
Pregnant or nursing women
Hypersensitivity to Trabectedin or any excipient in prior cycles

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01303094

Contacts

Contact: Nicolas PENEL, MD, PhD	03.20.29.59.20	n-penel@o-lambret.fr
Contact: Yvette VENDEL, CRA	03.20.29.59.40	y-vendel@o-lambret.fr

Locations

France
Saint-Jacques Hospital	Recruiting
Besancon, France, 25 000
Contact: Elsa KALBACHER, MD +33 (0)3.81.66.87.05 ekalbacher@gmail.com
Principal Investigator: Elsa KALBACHER, MD
Sub-Investigator: Loïc CHAIGNEAU, MD
Institut Bergonié	Recruiting
Bordeaux, France, 33076
Contact: Antoine ITALIANO, MD, PhD 05 56 33 32 44 italiano@bergonie.org
Principal Investigator: Antoine ITALIANO, MD
Sub-Investigator: Binh Nguyen BUI, MD
Centre François Baclesse	Recruiting
Caen, France, 14076
Contact: Corinne DELCAMBRE, MD 02 31 45 50 15 c.delcambre@baclesse.fr
Principal Investigator: Corinne DELCAMBRE, MD
Sub-Investigator: Sabine NOAL, MD
Centre Jean Perrin	Recruiting
Clermont Ferrand, France, 63011
Contact: Jacques-Olivier BAY, MD 04 73 27 80 00 olivier.bay@cjp.fr
Principal Investigator: Jacques-Olivier BAY, MD, PhD
Sub-Investigator: Pascale DUBRAY, MD
Centre Georges François Leclerc	Recruiting
Dijon, France, 21079
Contact: Nicolas ISAMBERT, MD 03 80 73 75 06 nisambert@cgfl.fr
Principal Investigator: Nicolas ISAMBERT, MD
Centre Oscar Lambret	Recruiting
Lille, France, 59020
Contact: Nicolas PENEL, MD +33(0)320295918 n-penel@o-lambret.fr
Contact: Yvette VENDEL, CRA +33(0)320295940 y-vendel@o-lambret.fr
Principal Investigator: Nicolas PENEL, MD
Sub-Investigator: Antoine ADENIS, MD, PhD
Sub-Investigator: Dominique HOGUET, MD
Sub-Investigator: Annick CHEVALIER-PLACE, MD
Sub-Investigator: Anne LESOIN, MD
Sub-Investigator: Edith VANLERENBERGHE, MD
Centre Léon Bérard	Recruiting
Lyon, France, 69008
Contact: Isabelle RAY-COQUARD, MD 04 78 78 28 88 raycoqua@lyon.fnclcc.fr
Principal Investigator: Isabelle RAY-COQUARD, MD
Sub-Investigator: Jean-Yves BLAY, MD, PhD
Léon Bérard Center	Recruiting
Lyon, France, 69 008
Contact: Isabelle RAY COQUART, MD +33 (0)4.78.78.28.88 blay@lyon.fnclcc.fr
Principal Investigator: Isabelle RAY COQUART, MD PhD
Sub-Investigator: Jean Yves BLAY, MD PhD
Sub-Investigator: Pierre BIRON, MD
Sub-Investigator: Marie GHELGHOUM, MD
Sub-Investigator: Pierre HEUDEL, MD
Sub-Investigator: Philippe CASSIER, MD
Sub-Investigator: Olfa DERBEL, MD
CHU Timone Adultes	Recruiting
Marseille, France, 13385
Contact: Florence DUFFAUD, MD 04 91 38 57 08 fduffaud@ap-hm.fr
Principal Investigator: Florence DUFFAUD, MD
Sub-Investigator: Sébastien SALAS, MD
Sub-Investigator: Thanh- Khoa HUYNH, MD
Paoli Calmette Institute	Recruiting
Marseille, France, 13 273
Contact: François BERTUCCI, MD +33 (0)4.91.22.37.89 bertucci@marseille.fnclcc.fr
Principal Investigator: François BERTUCCI, MD
Sub-Investigator: Anthony GONCALVES, MD
Sub-Investigator: Jean Marc EXTRA, MD
Centre Antoine Lacassagne	Recruiting
Nice, France, 06189
Contact: Antoine THYSS, MD, PhD 04 92 03 16 13 antoine.thyss@nice.fnclcc.fr
Principal Investigator: Antoine THYSS, MD, PhD
Sub-Investigator: Lauris GASTAUD, MD
Institut Curie	Recruiting
Paris, France, 75005
Contact: Sophie PIPERNEAU-NEUMANN, MD 01 44 32 42 76 sophie.piperno-neumann@curie.net
Principal Investigator: Sophie PIPERNEAU-NEUMANN, MD
Sub-Investigator: Valérie LAURENCE, MD
Sub-Investigator: Laurent MIGNOT, MD
Tenon Hospital	Recruiting
Paris, France, 75 020
Contact: Jean Pierre LOTZ, MD jean-pierre.lotz@tnn.aphp.fr
Principal Investigator: Jean Pierre LOTZ, MD
Sub-Investigator: Danièle AVENIN, MD
Sub-Investigator: Frédéric SELLE, MD
Sub-Investigator: Joseph GLIGOROV, MD
Sub-Investigator: Karine BEERBLOCK, MD
Sub-Investigator: Domnita BURCOVEANU, MD
Sub-Investigator: Ahmed KHALIL, MD
Centre Henri Becquerel	Recruiting
Rouen, France, 76038
Contact: Cécile GUILLEMET, MD 02 32 08 22 38 cecile.guillemet@rouen.fnclcc.fr
Principal Investigator: Cecile GUILLEMET, MD
Sub-Investigator: Marianne LEHEURTEUR, MD
Sub-Investigator: Olivier RIGAL, MD
Sub-Investigator: Corinne VEYRET, MD
Sub-Investigator: Isabelle TENNEVET, MD
Sub-Investigator: Frédéric DI FIORE, MD
Institut Claudius Regaud	Recruiting
Toulouse, France, 31052
Contact: Christine CHEVREAU, MD 05 61 42 41 74 chevreau@icr.fnclcc.fr
Principal Investigator: Christine CHEVREAU, MD
Sub-Investigator: Yann BERGE, MD
Sub-Investigator: Ewa COTTURA, MD
Sub-Investigator: Carlos-Alberto GOMEZ-ROCA, MD
Institut Gustave Roussy	Recruiting
Villejuif, France, 94805
Contact: Axel LE CESNE, MD 01 42 11 43 16 axel.lecesne@igr.fr
Principal Investigator: Axel LE CESNE, MD
Sub-Investigator: Aurore BLESIUS, MD
Sub-Investigator: Julien DOMONT, MD
Sub-Investigator: Patricia PAUTIER, MD

Sponsors and Collaborators

Centre Oscar Lambret

Groupe Sarcome Français

Groupe d’études des Tumeurs Osseuses

Investigators

Principal Investigator:

Nicolas PENEL, MD, PhD

Centre Oscar Lambret

More Information

No publications provided

Responsible Party:	Centre Oscar Lambret
ClinicalTrials.gov Identifier:	NCT01303094 History of Changes
Other Study ID Numbers:	T-DIS-1001
Study First Received:	February 23, 2011
Last Updated:	August 7, 2012
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:

Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Trabectedin
Antineoplastic Agents, Alkylating

Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013

Continuing vs Intermittent Trabectedin-regimen in Patients With Advanced Soft Tissue Sarcoma Experiencing Response or Stable Disease After the 6th Cycle (T-DIS)